Background: Immune checkpoint inhibitors (ICI) are the new standard of care for some MSI/dMMR advanced tumors in first-line setting or after progression under conventional chemotherapy. Frequency of MSI/dMMR increasing with age, the tolerability and efficacy of ICIs in elderly patients, appears as a crucial clinical issue. We aimed to evaluate the tolerability and efficacy of ICIs in ≥ 75 years patients with metastatic MSI/dMMR gastro-intestinal (GI) cancer. Methods: All pts with MSI/dMMR metastatic GI cancer treated by anti-PD1 ± anti-CTLA4 without concomitant chemotherapy at Saint-Antoine hospital and included in our prospective, monocenter cohort, were analyzed. Pts were divided into the elderly (≥75 years) and non-elderly (<75 years) groups. The incidence and evolution of grade ≥ 3 immune-related adverse events (irAE) and grade ≥ 2 endocrine adverse events were evaluated. Secondary objectives were progression-free survival (PFS) and overall survival (OS) regarding age and the occurrence of irAEs. Results: Two hundred and one patients were included: 24 pts≥75 years (75 to 90 years) and 177 pts< 75 years (22 to 74 years). 171 (79%) had mCRC. In the entire population, the incidence of irAEs was 40.5% with anti-PD1 plus anti-CTLA4 and 23% with anti-PD1 monotherapy (p= 0.011). Combination of anti-PD1 and anti-CTLA4 were administered to 29% of the elderly group and 40% of the non-elderly group. There was no statistical difference in the incidence of irAEs between the two populations (37.5% in the elderly group vs 29% in the non-elderly group; p=0.48) neither in their type (12% vs 7% of hepatic cytolysis, 13% vs 16% of endocrine irAEs) or management (17% vs 19% corticosteroid therapy, 21% and 16% of ICI discontinuation). No significant difference was observed between elderly/non elderly for PFS (HR 0.91, 95%CI 0.40-2.06; p=0.83) and OS (HR 1.6, 95%CI 0.65-3.96; p= 0.21). Pts experiencing irAEs had superior survival outcomes than those without irAEs (PFS HR 2.93, 95%CI 1.69-5.09; p=0.02 and OS HR 2.05, 95%CI 1.13-3.74; p=0.045) in the whole cohort (n=201). Conclusions: Tolerability and efficacy of ICIs for pts with MSI/dMMR GI cancers are similar for elderly compare as for non-elderly pts. Pts experiencing irAEs had superior survival outcomes. Further prospective studies with systematic geriatric assessment are required to evaluate the tolerability of ICIs especially for frail elderly pts.